Tislelizumab Combined With Pemetrexed/ Carboplatin in Patients With Brain Metastases of Non-squamous NSCLC

• ClinicalTrials.gov Identifier: NCT04507217
• Recruitment Status: Not yet recruiting
• First Posted: August 11, 2020
• Last Update Posted: August 14, 2020
• Sponsor: Sun Yat-sen University
• Information provided by (Responsible Party): Li Zhang, MD, Sun Yat-sen University

Tracking Information

• First Submitted Date: August 6, 2020
• First Posted Date: August 11, 2020
• Last Update Posted Date: August 14, 2020
• Estimated Study Start Date: September 1, 2020
• Estimated Primary Completion Date: September 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2020)

Progression-Free Survival (PFS) rate at 12 months according to RECIST v1.1 [ Time Frame: 12months ]

Progression-free survival is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first

Original Primary Outcome Measures (submitted: August 6, 2020)

PFS rate at 12 months [ Time Frame: 12months ]

Progression-Free Survival (PFS) rate at 12 months according to RECIST v1.1 Progression-free survival is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first.

Current Secondary Outcome Measures (submitted: August 12, 2020)

• Objective Response Rate (ORR) according to RECIST v1.1 [ Time Frame: 36 months ]
  ORR is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR).
• Progression-free survival (PFS) according to RECIST v1.1 [ Time Frame: 36 months ]
  Progression-free survival is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first.
• Overall Survival (OS) [ Time Frame: 36 months ]
  OS is defined as the time from the starting date of study drug to the date of death due to any cause
• Progression-free survival 2 (PFS2) [ Time Frame: 36 months ]
  PFS2 is defined as the time from first intracranial disease progression to second/subsequent disease progression (intracranial or extracranial) after initiation of new anti-cancer therapy, or death from any cause, whichever occurs first
• Duration of Response (DoR) according to RECIST v1.1 [ Time Frame: 36 months ]
  DoR is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) to the date of first documented of disease progression or death, whichever occurs first
• Incidence and severity of treatment-emergent AEs (TEAEs) [ Time Frame: 36 months ]
  TEAEs graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
• Neurocognitive impairment [ Time Frame: 36 months ]
  Neurocognitive impairment according to Hopkins Verbal Learning Test-Revised（HVLT-R）

Original Secondary Outcome Measures (submitted: August 6, 2020)

• ORR [ Time Frame: 36 months ]
  Objective Response Rate (ORR) according to RECIST v1.1 ORR is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR).
• Progression-free survival (PFS) [ Time Frame: 36 months ]
  Progression-free survival is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death
• OS [ Time Frame: 36 months ]
  OS is defined as the time from the starting date of study drug to the date of death due to any cause.
• Progression-free survival 2 (PFS2) of patients who have only intracranial PD at first in Cohort1 according to RECIST v1.1 [ Time Frame: 36 months ]
  PFS2 is defined as the time from first intracranial disease progression to second/subsequent disease progression (intracranial or extracranial) after initiation of new anti-cancer therapy, or death from any cause, whichever occurs first.
• Duration of Response (DoR) according to RECIST v1.1 [ Time Frame: 36 months ]
  DoR is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) to the date of first documented of disease progression or death, whichever occurs first.
• Incidence and severity of treatment-emergent AEs (TEAEs) graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 [ Time Frame: 36 months ]
  • Incidence and severity of treatment-emergent AEs (TEAEs) graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
• Neurocognitive impairment according to Hopkins Verbal Learning Test-Revised（HVLT-R） [ Time Frame: 36 months ]
  • Neurocognitive impairment according to Hopkins Verbal Learning Test-Revised（HVLT-R）

Current Other Pre-specified Outcome Measures (submitted: August 12, 2020)

• PD-L1 expression, TMB, and other potential predictive biomarkers, correlated with response to treatment [ Time Frame: 36 months ]
• Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1 and RANO-BM [ Time Frame: 36 months ]

Original Other Pre-specified Outcome Measures (submitted: August 6, 2020)

• • PD-L1 expression, TMB, and other potential predictive biomarkers, correlated with response to treatment [ Time Frame: 36 months ]
  • PD-L1 expression, TMB, and other potential predictive biomarkers, correlated with response to treatment
• • Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1 and RANO-BM [ Time Frame: 36 months ]
  • Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1 and RANO-BM

Descriptive Information

• Brief Title: Tislelizumab Combined With Pemetrexed/ Carboplatin in Patients With Brain Metastases of Non-squamous NSCLC
• Official Title: A Phase II, Open-Label, Multicenter, Prospective Clinical Study to Investigate the Efficacy and Safety of Tislelizumab Combined With Pemetrexed/ Carboplatin in Patients With Brain Metastases of Non-squamous Non-small Cell Lung Cancer
• Brief Summary: This is a phase II, Open-Label, Multicenter, Prospective Clinical Study to Investigate the Efficacy and Safety of Tislelizumab Combined with Pemetrexed/ Carboplatin in Patients with Brain Metastases of Non-squamous Non-small Cell Lung Cancer. The primary end point is PFS, and secondary endpoint is ORR, OS, DoR and Neurocognitive impairment. during the study, the exploratory objectives including (1) PD-L1 expression, TMB, and other potential predictive biomarkers, correlated with response to treatment (2) Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1 and RANO-BM
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

Tislelizumab Combined with Pemetrexed/ Carboplatin

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• NSCLC Stage IV
• Brain Metastases
• PD-1 Antibody

Intervention

Drug: Tislelizumab, Carboplatin, Pemetrexed

Tislelizumab: 200mg administered intravenously (IV) on Day 1 of each 21-day cycle

Carboplatin: AUC 5 administered intravenously (IV) on Day 1 of each 21-day cycle, 4 cycles

Pemetrexed: 500mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle

Study Arms

• Experimental: BM without prior radiotherapy
  • No Prior Systemic treatment for Stage IV NSQ-NSCLC
  • With asymptomatic untreated BM
  Intervention: Drug: Tislelizumab, Carboplatin, Pemetrexed
• Experimental: BM with prior radiotherapy
  • No Prior Systemic treatment for Stage IV NSQ-NSCLC
  • With Clinical stable BM with prior radiotherapy
  Intervention: Drug: Tislelizumab, Carboplatin, Pemetrexed

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: August 6, 2020): 78
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 1, 2023
• Estimated Primary Completion Date: September 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Histologically confirmed metastatic (Stage IV) not amenable to curative surgery or radiotherapy, non-squamous NSCLC according to American Joint Committee on Cancer, 8th Edition.
2. Imaging confirmed brain metastases
3. No prior systemic treatment for metastatic NSCLC
4. Subjects with asymptomatic untreated brain metastases: no neurological symptoms, no requirements for corticosteroids, no surrounding edema, and no lesion >1.5 cm)
5. Subjects with previously treated brain metastases: clinically stable for at least 2 weeks, have no evidence of new or enlarging brain metastases, and be off steroids 3 days prior to trial initiation as per local site assessment.
6. ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.
7. Have at least one measurable extracranial target lesion (per RECIST 1.1)
8. Life expectancy ≥ 3 months
9. Have adequate organ function as indicated by the following laboratory values

Exclusion Criteria:

1. Received prior therapies targeting PD-1, PD-L1, CTLA-4 or other immune checkpoints inhibitors.
2. Received prior systemic cytotoxic chemotherapy for advanced disease
3. Have activating EGFR mutations or ALK gene rearrangements
4. Have brain metastases that is suitable for surgical resection
5. Treatment with any approved systemic anti-cancer therapy or systemic immune-stimulatory agents (including but not limited to interferons, interleukin IL-2, and tumor necrosis factor) within 28 days prior to initiation of study treatment.
6. Clinically uncontrolled pleural effusion or ascites that requires pleurocentesis or abdominal tapping for drainage within 2 weeks prior to initiation of study treatment.
7. Have Active leptomeningeal metastasis.
8. History of allergic reactions to any study drugs.
9. CrCl < 45 mL/min
10. Patients with active viral hepatitis that requires treatment.
11. Active autoimmune diseases that requires treatment and may affect study treatment estimated by investigator.
12. Any condition that required systemic treatment with either corticosteroids or any other immunosuppressive medication that may affect study treatment estimated by investigator.
13. Severe chronic or active infections requiring systemic antibacterial, anti-fungal or antiviral therapy.
14. With a history of interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc.
15. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that would be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs (Adverse Events) or result in insufficient or might impair compliance with study conduct.
16. Concurrent participation in another clinical study.
17. Pregnant, breastfeed, or expect to conceive or father children within the projected duration of the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Li Zhang, Master; +86-13902282893; zhangli@sysucc.org.cn

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04507217
• Other Study ID Numbers: BGB-A317-2003-IIT
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Li Zhang, MD, Sun Yat-sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Sun Yat-sen University
• Verification Date: August 2020